Our laboratory has demonstrated a ladder-like network of enkephalin (Enk) fibers in thoracolumbar spinal cord coinciding with the distribution of preganglionic sympathetic nuclear regions and that these Enk fibers are of both supraspinal and intraspinal origin. An objective of the proposed investigation is to extend our previous work to determine the origins of descending Enk brainstem projections to spinal sympathetic nuclei using retrograde transport-immunocytochemical techniques and the anterograde transport of radiolabeled amino acids or HRP-WGA. These Enk pathways may participate in the augmented sympathetic activity that attends opiate withdrawal. We plan to describe the distribution of the different types of opioid receptors in thoracolumbar spinal cord in adulthood and during ontogeny using in vitro receptor autoradiography and to test the hypothesis that single or multiple opioid receptor types are involved in the expression of sympathetic functions as a response to physical stress (cold exposure, immunobilization) or chemical stress (reserpine treatment, opiate dependence and withdrawal). Specifically, we would like to determine whether the location of Enk containing brainstem neurons projecting to restricted spinal cord segments or sympathetic nuclei can be correlated with anatomical/functional subunits of sympathetic outflow. In addition, quantification of the mu, delta, and kappa opioid receptors within spinal sympathetic nuclei will be examined throughout postnatal development, adulthood, and subsequent to stress paradigms which challenge the sympathetic nervous system.